Recent Developments in Protein Lactylation in PTSD and CVD: Novel Strategies and Targets

Abstract

In 1938, Corneille Heymans received the Nobel Prize in physiology for discovering that oxygen sensing in the aortic arch and carotid sinus was mediated by the nervous system. The genetics of this process remained unclear until 1991 when Gregg Semenza while studying erythropoietin, came upon hypoxia-inducible factor 1, for which he obtained the Nobel Prize in 2019. The same year, Yingming Zhao found protein lactylation, a posttranslational modification that can alter the function of hypoxia-inducible factor 1, the master regulator of cellular senescence, a pathology implicated in both post-traumatic stress disorder (PTSD) and cardiovascular disease (CVD). The genetic correlation between PTSD and CVD has been demonstrated by many studies, of which the most recent one utilizes large-scale genetics to estimate the risk factors for these conditions. This study focuses on the role of hypertension and dysfunctional interleukin 7 in PTSD and CVD, the former caused by stress-induced sympathetic arousal and elevated angiotensin II, while the latter links stress to premature endothelial cell senescence and early vascular aging. This review summarizes the recent developments and highlights several novel PTSD and CVD pharmacological targets. They include lactylation of histone and non-histone proteins, along with the related biomolecular actors such as hypoxia-inducible factor 1α, erythropoietin, acid-sensing ion channels, basigin, and Interleukin 7, as well as strategies to delay premature cellular senescence by telomere lengthening and resetting the epigenetic clock.

Clinical characteristics and 1-year all-cause mortality in elderly hip fracture patients with type 2 diabetes mellitus: a propensity score matching study

“…As an acute phase protein, CRP can directly re ect the degree of in ammatory stress and endothelial damage in patients with fractures, and higher CRP levels in T2DM group suggested perioperative post-traumatic stress and in ammatory stimulation, etc. increase the heart burden 38 , and cause cardiac complications once decompensation 39 . (2) T2DM patients are often combined with renal function damage, resulting in a decrease in the kidneys' ability to regulate uid and acid-based balance 40 , which is easy to induce water, electrolyte and acid-base imbalance, and even interfere with myocardial electrical activity and cause serious complications such as arrhythmia 41 .…”